A losing battle?

Study shows that weight loss through exercise triggers an increase in the appetite-stimulating hormone ghrelin

Feb. 3, 2005

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By BARBARA BERG

A new Fred Hutchinson/UW study provides insight into why weight loss through exercise is a challenge.

Photo by Todd McNaught

For those who plan to work off holiday weight gain with a few extra trips to the gym, keeping those pounds off may be harder than you think.

A new Fred Hutchinson and University of Washington study reveals that levels of an appetite-stimulating hormone rise in women who lose weight through exercise — even when they don't cut back on calories. Previous research has found the same hormone, called ghrelin, also is elevated in people who lose weight through dieting.

The new study was published Dec. 4 on line in the Journal of Clinical Endocrinology and Metabolism.

The findings support a growing body of evidence that the human body attempts to protect itself from weight loss by increasing the urge to eat. While this adaptation may have been essential for survival during times of famine, the same response, combined with today's abundance of high-calorie food, has likely contributed to the current obesity epidemic.

Weighty resistance

"Researchers have found that weight loss triggers an adaptive response in the body to resist further weight loss," said Dr. Anne McTiernan, a co-investigator of the study and member of the Public Health Sciences Division. McTiernan is the principal investigator of Physical Activity for Total Health (PATH) study, whose participants provided blood samples for the analysis.

Ghrelin is a hormone that is released into the bloodstream by the stomach and small intestine. It is the only substance manufactured by the body known to stimulate appetite and is one of only a few agents of any kind shown to increase appetite and food intake when it is injected into humans. In 2002, Dr. David Cummings, UW associate professor of medicine and corresponding author of the new study, found that ghrelin levels increase in obese individuals who lose weight through dieting.

In the new study, McTiernan and colleagues monitored weight loss and ghrelin levels in a group of 173 overweight, postmenopausal women who were randomly assigned to participate in either a yearlong aerobic-exercise program or a stretching program. Prior to their participation in the PATH study, none of the women exercised regularly.

Exercisers took part in a minimum of five 45-minute aerobic-activity sessions each week for a year, which included activities such as walking, bicycling and aerobics. Women in the stretching group attended once-weekly, 45-minute stretching sessions for a year and were asked not to change other exercise habits during the study. Both groups were strictly instructed to maintain their usual diets and were asked to complete questionnaires about their food intake.

Women's weight was measured and blood samples were collected at the start of the study and after three and 12 months. Cummings and Dr. Karen Foster-Schubert, the paper's primary author,measured ghrelin levels in the blood serum.

The researchers found that after a year, exercisers had lost an average of three pounds, while stretchers had no change in their weight. Weight loss in the exercise group was associated with a progressive increase in ghrelin levels, reaching about 18 percent over baseline levels after a year. The increased ghrelin levels also correlated with decreases in body-mass index (a calculation based on weight and height), waist circumference and total-fat mass. There was no change in ghrelin levels among women in the stretching group.

McTiernan said that while scientists do not yet understand how weight loss triggers an increase in circulating ghrelin levels, "this research provides some insight into why weight loss may be difficult in some people, which underscores the importance of not putting on extra pounds over the years."

The study was funded by the National Institutes of Health. Co-authors included Kumar Rajan, Dr. Yutaka Yasui and Dr. Shelley Twororger, all of the PHS Division, and colleagues at the V.A. Puget Sound Health Care System and the University of Colorado.

Study participants needed for two breast-health studies

The Effect of Aspirin on Mammograhic Density Study

Could taking an aspirin a day reduce breast density and thus make it easier for doctors to interpret mammograms? Center researchers seek to recruit 144 local women for a study to find out. The study is funded by the National Cancer Institute and the Avon Foundation.

Those eligible are women between 18 and 75 years old with higher-than-average breast density who have not taken hormonal contraceptives or hormone-replacement therapy within the past six months.

Participants will be randomly assigned to receive either aspirin or an identical-looking placebo pill. All participants will require two clinic visits; a brief physical exam, including a breast exam; a fasting blood draw and two mammograms. Participants also will be asked to fill out some questionnaires at the beginning and end of the study. For more information, call the Effect of Aspirin on Mammographic Density Study line at (206) 667-1391 or e-mail team@fhcrc.org.

Nutrition and Exercise for Women (NEW) Study

What are the effects of exercise and nutrition on breast-cancer risk factors?

Public Health Science Division researchers seek more than 500 Seattle-area participants for this National Cancer Institute-funded study. Needed are healthy overweight and sedentary postmenopausal women (ages 50 to 75) who live in the Seattle area and are willing to travel to Fred Hutchinson for a yearlong exercise or nutrition intervention.

Eligibility requirements include being a nonsmoker, not using hormone therapy for the past six months, getting less than an hour of moderate activity per week, and having a body mass index of 25 or greater.

Those who qualify must be willing to not participate in any other exercise or weight-loss programs during the 12-month study enrollment and must be willing to be randomly assigned to one of four following groups:

Moderate-intensity aerobic exercise for 45 minutes a day, five days per week for a year.

A reduced-calorie diet for a year.

Aerobic exercise and a reduced-calorie diet for a year.

No intervention (to serve as a control, or comparison, group).

At the end of the yearlong study, these women will receive a free, two-month pass to the center's state-of-the-art exercise facility and get to work out under the supervision of a personal trainer. They can also attend four group weight-loss meetings and receive a variety of educational handouts about diet and exercise.

To learn more, call the NEW Study-information line at (206) 667-6444 or e-mail new@fhcrc.org.

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